PLATELETS AND THROMBOPOIESIS Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A
نویسندگان
چکیده
1National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; 2Department of Medicine, Duke University Medical Center, Durham, NC; 3Office of Research Services, Division of Veterinary Resources, 4National Eye Institute, and 5National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD; 6Medical Service, Durham Veterans Affairs Medical Center, Durham, NC; and 7National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD
منابع مشابه
Regular Article PLATELETS AND THROMBOPOIESIS Q:A1 Myosin-II repression favors pre/proplatelets but shear activation generates platelets and fails in macrothrombocytopenia
• Myosin-II inhibition (with blebbistatin) and MYH9-RD mutations enhance shear fragmentation to pre/ proplatelet sizes. • Sustained shear activates normal myosin-II, which then favors division of pre/ proplatelets to smaller platelets. Megakaryocyte ploidy and the generation of pre/proplatelets are both increased in culture by pharmacologic inhibition of myosin-II, but nonmuscle myosin-IIA (MII...
متن کاملAbnormal megakaryocyte morphology and proplatelet formation in mice with megakaryocyte-restricted MYH9 inactivation.
Mutations in the MYH9 gene encoding nonmuscle myosin IIA lead to macrothrombocytopenia as observed in MYH9-related disorders. We used mice with megakaryocyte-restricted MYH9 inactivation to explore the role of myosin in thrombopoiesis. In situ, bone marrow MYH9Delta megakaryocytes were irregularly shaped, appearing leaky with poorly defined limits. The demarcation membranes were abnormally orga...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Asp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome
May-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), Sebastian syndrome (SBS), and Epstein syndrome (EPS) are a group of rare, autosomal dominant disorders characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies, together with variable manifestations of Alport-like symptoms that include high-tone sensorineural deafness, cataracts, and nephritis. These disorders resul...
متن کاملAsp1424Asn MYH9 mutation results in an unstable protein responsible for the phenotypes in May-Hegglin anomaly/Fechtner syndrome.
May-Hegglin anomaly (MHA), Fechtner syndrome (FTNS), Sebastian syndrome (SBS), and Epstein syndrome (EPS) are a group of rare, autosomal dominant disorders characterized by thrombocytopenia, giant platelets, and Döhle-like inclusion bodies, together with variable manifestations of Alport-like symptoms that include high-tone sensorineural deafness, cataracts, and nephritis. These disorders resul...
متن کاملThe May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway.
The gene implicated in the May-Hegglin anomaly and related macrothrombocytopenias, MYH9, encodes myosin-IIA, a protein that enables morphogenesis in diverse cell types. Defective myosin-IIA complexes are presumed to perturb megakaryocyte (MK) differentiation or generation of proplatelets. We observed that Myh9(-/-) mouse embryonic stem (ES) cells differentiate into MKs that are fully capable of...
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